The enzymatic mechanism of the first enzyme in histidine biosynthesis, ATP-phosphoribosyltransferase, will be studied using stopped flow and steady state techniques. The conformational and dissociative equilibria of a feedback supersensitive mutant will be compared to those of wild-type enzyme to study histidine inhibition. The alpha-secondary tritium and primary C14 isotope effects on the reaction will be separately determined as a function of histidine inhibition.